Erythropoiesis is an essential process for maintaining the homeostasis of the number of red blood cells. Human red blood cells have an average life span of approximately 120 days. Because senescent red blood cells are continuously removed from the circulatory system, approximately 100 billion red blood cells are newly produced every day in an adult body. The homeostasis of erythropoiesis is primarily maintained by erythropoietin (EPO), which is a hematopoietic factor. EPO is mainly produced by the kidney and circulates in the blood, and acts on committed erythroid progenitor cells (CFU-E) in the bone marrow to stimulate the proliferation and differentiation of these cells, thereby promoting erythropoiesis. When EPO production falls below the normal level, a shortage of EPO occurs, which causes a decrease in CFU-E and a reduction in erythropoiesis, leading to anemia. Anemia is a pathological condition in which insufficient hemoglobin concentration fails to meet the body's oxygen transport demands, and is associated with clinical symptoms such as decreased motivation for work, fatigability, shortness of breath, dizziness, and palpitation. Therefore, amelioration of symptoms is desired. Various types of diseases are known to cause anemia due to EPO deficiency, among which the most common is kidney disease. Patients with chronic renal failure exhibit renal anemia due to reduced EPO production caused by kidney damage. Many of the patients with chronic renal failure require frequent dialysis for renal function replacement, and approximately 90% of the patients on dialysis suffer anemia. At present, as a treatment method of renal anemia, the administration of recombinant human EPO (rHuEPO) is widely practiced. Many of the patients on dialysis receive rHuEPO, and many of them exhibit anemia-improving effects. However, because the administration of rHuEPO is a long-term treatment, it has problems such as an increase in cost.
Meanwhile, pluripotent cells such as embryonic stem cells (ES cells) and induced pluripotent stem cells (iPS cells), which are obtained by introducing undifferentiated cell-specific genes into somatic cells, have previously been reported (Patent Documents 1 and 2). In light of this, as a treatment method of renal anemia, a treatment method of transplanting EPO-producing cells, which are induced to differentiate from the aforementioned pluripotent stem cells, is under study. However, as of now, a technique for inducing the differentiation of EPO-producing cells from human pluripotent stem cells has not yet been fully established.